Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly
Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly
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DOI：
10.1128/mcb.20.17.6354-6363.2000
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发表时间：
2000-09-01
影响因子：
5.3
通讯作者：
Lim, L
中科院分区：
文献类型：
--
作者：
Zhao, ZS;Manser, E;Lim, L
p21激活的激酶PAK通过与PAK相互作用交换因子PIX的SH 3结构域相互作用而靶向焦点复合物（FC），Nck PIX是一种Rac GTP交换因子，其也结合称为GIT 1的G蛋白偶联受体激酶相互作用蛋白。GIT 1在成纤维细胞或上皮细胞中的过表达导致桩蛋白从FC损失并刺激细胞运动性。这是由于在PM的调节下，GIT 1的C末端125个残基结构域与桩蛋白的直接相互作用。在其激活状态下，GIT 1可以促进FC解体独立的肌动蛋白-肌球蛋白收缩事件。此外，GIT通过保守的Spa 2同源结构域直接偶联至FC的关键组分，粘着斑激酶（FAK）。我们认为GIT 1和FAK通过直接调节焦点复合物动力学和激活Rac来合作促进运动。
The p21-activated kinase PAK is targeted to focal complexes (FCs) through interactions with the SH3 domains of the PAK-interacting exchange factor PIX and Nck PIX is a Rac GTP exchange factor that also binds the G-protein coupled receptor kinase-interacting protein known as GIT1, Overexpression of GIT1 in fibroblasts or epithelial cells causes a loss of paxillin from FCs and stimulates cell motility. This is due to the direct interaction of a C-terminal 125-residue domain of GIT1 with paxillin, under the regulation of PM. In its activated state, GIT1 can promote FC disassembly independent of actin-myosin contractile events. Additionally, GIT directly couples to a key component of FCs, focal adhesion kinase (FAK), via a conserved Spa2 homology domain. We propose that GIT1 and FAK cooperate to promote motility both by directly regulating focal complex dynamics and by the activation of Rac.